The present invention relates to apparatus and methods for filling of liquid or solid particulate materials into receptacles.
More particularly, the present invention relates to apparatus for filling pharmaceutical dosage forms, such as, soft or hard gelatin capsules, with pharmaceutically active formulations, usually in the form of liquid or solid particulate materials, e.g. powders, granules or pellets, especially for use as pharmaceuticals. The present invention also relates to methods related thereto.
Capsule filling machines or encapsulation machines are commonly used, especially in the pharmaceutical industry, for filling empty soft or hard gelatin capsules with pharmaceutical formulations. Such pharmaceutical formulations may be in the form of solid particulate materials, such as powders, granules, pellets and the like.
Hard or soft gelatin capsules generally comprise two parts, a body and a cap. Capsule filling machines usually operate by first separation the caps from bodies; filling a volumetrically measured dose of the formulation into the separated body of the capsule of the gelatin capsules; re-joining the capsules, i.e. conjoining the capsule cap and body; and then ejection of the filled capsule from the capsule filling machines.
In addition, automated capsule filling machines will usually also comprise the ability to reject bad gelatin capsules, i.e. capsules which are broken or which are not paired, i.e. do not comprise a body and a cap.
Manual, hand operated capsule filling machines are known and are generally used in hospitals or pharmacies.
In the manufacture of pharmaceuticals, automated capsule filling machines are widely used. Modern capsule filling machines generally comprise a rotary carousel equipped with a plurality of operating stations for processing the capsules.
The filling method usually consists of the steps opening the empty capsules at a station where the capsule bodies are separated from the caps to form two separate rows of bodies and caps; filling a volumetrically metered quantity of the pharmaceutical formulation into each capsule body at a filling station; and closing each filled capsule by applying a cap to the respective body.
However, such machines generally suffer from dose variation in the receptacles, particularly when filling a wide range of solid products having a wide range of packing densities and/or physical characteristics making handling difficult, such as shear sensitive materials. Consequently, this may cause capsules being filled with different amounts of a formulation. This is particularly undesirable when the capsules are filled with dose sensitive pharmaceutical formulations that must be administered at a precise predetermined dose.
US Patent application No.
Therefore there still remains a need for a new apparatus and process for accurate and consistent filling of receptacles with a wide range of liquid or solid fill materials.
We have now found a device that overcomes or mitigates the problems associated with the prior art devices. More particularly, the present invention provides a receptacle filling system which provides accurate real time weight control of the material being filled into the receptacle.
Thus, according to a first aspect of the present invention there is provided an apparatus for filling a material into a receptacle (16), said apparatus comprising:
The pair of mating bushes will generally comprise a male bush and a female bush. In a preferred aspect of the invention the male bush is the body bush and the female bush is the closure bush.
The means for segregating compliant receptacles, e.g. accurately filled receptacles, from non-compliant receptacles, e.g. damaged or inaccurately filled receptacles, will generally comprise positioning the filled receptacle (in its body bush) on a weigh cell, capable of determining whether a receptacle is compliant or non-compliant; and transporting the body bush containing the receptacle adjacent to a respective hopper where the receptacle is ejected from the body bush into a compliance hopper or noncompliance hopper as appropriate. Means for ejecting the receptacle from the body bush may comprise one or more ejections posts, such that the body bush can be depressed against the one or more ejections posts, urging the receptacle from body bush.
It is the body bush that is temporarily attached and/ or detached from the bush pair handling system.
The material to be filled into the receptacle may be a liquid or a solid particulate material, e.g. in the form of powder, granules, pellets and the like. The material may also be combinations of forms of solid or liquid materials. The material may especially comprise a pharmaceutical material. It will be understood that the filling station may measure a dose of material to be filled into the receptacle gravimetrically or volumetrically, depending, inter alia, upon the nature of the material, etc. In one particular aspect of the invention the filling station measures the dose gravimetrically, for example, using real time weight control, such as the process described in
Thus, according to this aspect of the invention there is provided an apparatus for filling a material into a receptacle, as herein described, in combination with a material filler for accurately filling particulate material, for example a pharmaceutical substance, into a receptacle, the material doser comprising a hopper with a tip having an aperture through which powder may flow, a closure to close the aperture and a vibration device configured to agitate the hopper, wherein a first portion of the hopper is formed of flexible material and a second portion proximate the tip is formed of substantially rigid material.
Desirably, the means transporting the receptacle to and from a filling station is automated, for example, the means comprise a robotic arm which may be remotely controlled and/ or computer controlled. Such a robotic arm will be provided with at least one bush pair holder which is aligned with at least one bush pair, such that, the bush pair is capable of being separated in order to open the receptacle and/or re-associated enabling the receptacle to be reclosed. If the receptacle is a conventionally known gelatin capsule, then the body of the capsule will be retained in the body bush and the cap or closure of the capsule will be retained in the closure bush, which remains fixed to the receptacle holder.
The bushes may comprise a low friction material, such as a thermoplastic polyethylene, e.g. UHMWPE or a low friction coated material
In a further embodiment, the robotic arm may be provided with a plurality of bush pair holders and bush pairs. In a particular embodiment the robotic arm may be provided with a rotatory shaft rotatably connected to an extension arm, such that the extension arm is provided with a bush holder and receptacle holder at each end. Thus, the robotic arm may be provided with a pair of bush holders and receptacle holders or a plurality of pairs of bush holders and receptacle holders, e.g. 4, 6, 8, 10, or more bush holders and two part bush assemblies.
When the robotic arm is provided with one or more pairs of bush holders and receptacle holders the rotatable extension arm can be rotated about the shaft, providing dual bush exchange or dual receptacle filling, thus allowing parallel processing of the receptacle. This significantly speeds the filling process allowing filling rates of from about 100 to about 1,000 receptacles per hour to be filled.
Increasingly, patients are required to take more than one medicine and this is especially the case in the treatment of bronchial disorders with respiratory drugs. For example, combination therapies such as a steroid with a β2 agonist, e.g. fluticasone and salmeterol, have been commercially successful. Therefore, according to a further aspect of the invention, the robotic arm may be capable of visiting more than one filling site. Such an arrangement is particularly advantageous when it is desired to fill a receptacle with a combination therapy comprising more than one active ingredient.
Desirably, the body bush is designed to be only loosely held in the bush pair holder so that the body bush may be moved longitudinally and axially whilst being retained in the bush holder. This enables the receptacle to be inserted in, closed or ejected, from the bush pair
Thus, the bush holder is located at the end of the extension arm, and comprises a fork capable of being located about the body bush which allows the detachment of the bush from the extension arm.
The bush pair comprises a bush body and is provided with a circumferential shoulder, such that the fork at the end of the extension arm may wrap around the bush body and engage with the circumferential shoulder, enabling the bush to be located and lifted.
In a further variation not belonging to the invention the bush holder may be adapted to hold the body bush by means of a pneumatic vacuum cup, a vacuum shoe, gripper, a pneumatic gripper, an electric gripper or a magnet, as an alternative to the fork arrangement herein described, so that the body bush may be moved longitudinally whilst being retained in the bush pair holder.
In order to facilitate the alignment of the bush pair and the receptacle holder the and the opening and closing of the receptacle, the body bush and closure bush are provided with a corresponding chamfered surfaces, so that the bush and the receptacle holder can meet in a male/female arrangement.
According to an embodiment of the invention the receptacle and body bush may be weighed by a weighing system prior to being filled. This allows the system to determine whether a receptacle is present and/or whether a receptacle is damaged, for example if there is a hole in the capsule wall. A control system may be configured to operate the material dispenser only when the correct weight of receptacle is detected. In addition, the receptacle may be weighed by a weighing system during filling, this may enable the flow rate of the material dispenser to be altered during filling of the material, for example, the flow rate may be decreased as a predetermined target weight is approached.
In addition, the robotic arm may also be provided with a closure plate, generally mounted adjacent or above the bush pair holder, which facilitates the closure of the respectable after filling, providing a surface against which the receptacle can be abutted during re-closure of the receptacle.
The receptacle will generally be a hard or soft gelatin capsule. The capsule will usually be resiliently deformable so that the capsule can be opened and re-closed after filling.
According to a further aspect of the invention there is provided the use of an apparatus herein described for filling a receptacle, such as a hard or soft gelatin capsule, with a consistent dose of material.
According to a yet further aspect of the present invention there is provided a method of filling a receptacle (16) with a consistent dose of a material, wherein the method comprises the steps of
The invention will now be illustrated by way of example only and with reference to the accompanying figures in which:
Referring to
Bush pair handling system (6) is in the "open" position, in which a receptacle (capsule) (16) is shown to be separated into a capsule body (16a) and a capsule closure (16b). The capsule body (16a) is located in the body bush (10) and the capsule closure (16b) is located in the closure bush (8).
Bush pair handling system (7) is in the "closed" position, in which a receptacle (capsule) (17) is shown as a conjoined unit. The body bush (11) and the closure bush (9) are shown having been brought together; the capsule (17) is closed and urged into the closure bush (9), ready for transfer to means for segregating compliant receptacles from non-compliant receptacles, e.g. a weigh cell (not shown).
Referring to
The apparatus is provided with a capsule dispenser (20) and a filling system/material dispenser (21). The capsule dispenser is provided with a detachment column (22), said column (22) being provided with a bush locator spindle (23). A weigh cell (24) is located adjacent the filling system/material dispenser (21), generally below the bush pair handling system (6).
A recoupling pillar (25) is also provided. The apparatus also includes ejection posts (26a and 26b) adjacent a pair of hoppers (27a and 27b) for dispatching compliant (27a) and non-compliant (27b) capsules (not shown).
In use the robotic arm (1) delivers a bush pair handling system (6) to a detachment column (22) of the capsule dispenser (21) and locates the closure bush (8) and body bush (10) about the bush locator spindle (23).
The capsule dispenser (21) dispenses a capsule (17) from the dispenser (21) into the bushes (8/10). The robotic arm 1 then depresses the bush (8/10) against the
The invention will now be illustrated by way of example only and with reference to the accompanying figures in which:
Referring to
Bush pair handling system (6) is in the "open" position, in which a receptacle (capsule) (16) is shown to be separated into a capsule body (16a) and a capsule closure (16b). The capsule body (16a) is located in the body bush (10) and the capsule closure (16b) is located in the closure bush (8).
Bush pair handling system (7) is in the "closed" position, in which a receptacle (capsule) (17) is shown as a conjoined unit. The body bush (11) and the closure bush detachment column (22) urging the capsule closure (16b) into the corresponding closure bush (8), when pressure is released by the robotic arm (1), the closure bush (8) and the body bush (10) separate, leaving the capsule closure (16b) in the closure bush (8) and the capsule body (16a) in the body bush (10). The capsule body (16a) is then ready for filling.
The robotic arm (1) then collects the body bush (10) containing the capsule body (16a) and transfers it to the weigh cell (24) at the filling system/station (21). The capsule body (16a) is then filled to a gravimetrically predetermined amount and the robotic arm (1) retrieves the body bush (10) and delivers the body bush (10) and the closure bush (8) to the recoupling pillar (25). At the recoupling pillar (25) the robotic arm (1) depresses the bushes (8/10) between the recoupling pillar (25) and the closure plate (19). urging the body bush (10) and the closure bush (8) together, thus recoupling the capsule body(16a) and capsule closure (16b).
The robotic arm (1) then delivers the bushes (8/10) to one of the ejection posts (26a) or (26b), whereby the filled and recoupled capsule (17) is ejected into either the compliant hopper (27a) or non-compliant hopper (27b).
Providing a bush pair handling system (6 and 7) at each end (4 and 5) of the robotic arm (1) enables the robot (18) to continually process capsules, i.e. collecting another capsule whilst one capsule is being filled.
This list of references cited by the applicant is for the reader's convenience only. It does not form part of the European patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be excluded and the EPO disclaims all liability in this regard.